title: IL-1β strikingly enhances antigen-driven CD4 and CD8 T-cell responses.
abstract: Protective immune response requires massive expansion of antigen-triggered naïve cells, extensive differentiation into effector cells, migration of effectors into the periphery, and generation of a functional memory compartment. IL-1β strikingly enhances expansion of antigen-primed CD8 and CD4 T cells in vivo. Its T-cell expansion in lymph nodes and spleen was direct, requiring that the stimulated T cells express IL-1R1. Immunization in the presence of IL-1β increases the frequency of IL-17- and IFN-γ-producing cells among primed CD4 cells and the frequency of granzyme B-expressing and IFN-γ-producing cells and of cytotoxic cells among primed CD8 cells. IL-1β-induced increase in the number of the activated CD4 and CD8 cells and augmented differentiation of the antigen-triggered T cells is very pronounced in liver and lungs. CD4 and CD8 cells primed in the presence of IL-1β display augmented cell number and enhanced cytokine production when rechallenged 2 mo after priming with antigen and lipopolysaccharide (LPS). In five in vivo models, IL-1β enhanced the protective value of weak vaccines. Preliminary analysis of in vivo gene expression in CD4 cells stimulated with IL-1β revealed that IL-1β caused gene expression changes consistent with the up-regulation of pathways involved in cell replication, cell survival, and enhanced energy metabolism. Thus, IL-1β enhances antigen-primed CD4 and CD8 T-cell expansion, differentiation, and migration to the periphery and memory, the specific functions required for generation of effective protective immune responses.
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1892 Lautenberg Center for General and Tumor Immunology, The Hebrew University/Hadassah Medical Center, Jerusalem 91120, Israel.
authors.forename: S Z
authors.initials: SZ
authors.lastname: Ben-Sasson
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1892.
authors.forename: K
authors.initials: K
authors.lastname: Wang
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1892.
authors.forename: J
authors.initials: J
authors.lastname: Cohen
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1892.
authors.forename: W E
authors.initials: WE
authors.lastname: Paul
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D007249:Inflammation; D020381:Interleukin-17 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D053573:Receptors, Interleukin-1 Type I / Q000378:metabolism; D014612:Vaccines
chemical_list: C583355:IL1R1 protein, mouse; D020381:Interleukin-17; D053583:Interleukin-1beta; D053573:Receptors, Interleukin-1 Type I; D014612:Vaccines; D049452:Green Fluorescent Proteins